Oestrogen, brain function, and neuropsychiatric disorders
- Division of Psychological Medicine, Box P050, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK
- Correspondence to: R Norbury;
Oestrogen has multiple effects on brain function
There is an increasing amount of research on the neurobiological effects of oestrogen. Also, health professionals are being asked for guidance on whether women should be prescribed oestrogen and progestogen hormone replacement therapy (HRT) not only to treat vasomotor instability and reduce bone loss, but also in various neuropsychiatric disorders. However, it is controversial whether oestrogen is indicated in the treatment of disorders such as depression, Alzheimer’s disease, and schizophrenia. A recent large scale study examining the effects of HRT, funded by the National Institutes of Health (NIH) in the USA, was prematurely terminated owing to increased rates of breast cancer, heart disease, and stroke.1 Shortly afterwards, the WISDOM trial funded by the MRC in the United Kingdom was also terminated. This has reinforced the need to have solid indications for the use of oestrogen-only replacement therapy.
OESTROGEN AS A NEUROPROTECTANT
Oestrogens affect the development and aging of brain regions that are crucial to higher cognitive functions (like memory) and are implicated in neuropsychiatric disorders such as Alzheimer’s disease. For example, oestrogens increase synaptic and dendritic spine density in the hippocampus. In rats, oophrectomy results in a decrease in dendritic spine density in CA1 pyramidal cells, but this is prevented by the administration of oestrogens. Moreover, synaptic spine density is related to circulating oestradiol levels.2 Until recently it was unclear how these oestrogen induced dendritic changes affected neuronal function. However, it has now been shown that oestrogen induces an increase in N-methyl-D-aspartate (NMDA) receptors in rat hippocampal neurones in the same region where an increase in dendritic spines is found, suggesting that the “new” oestrogen-induced spines are excitatory.3,4
Among the most biologically plausible explanations why HRT might ameliorate age associated deficits in memory are modulatory effects on the cholinergic system in brain regions …